On Saturday, India's Serum Institute of India (SII), which has partnered with British pharma giant AstraZeneca for manufacturing the Oxford vaccine candidate for COVID-19, sought permission from the Drugs Controller General of India (DCGI) for conducting Phase II and III human clinical trials of the potential vaccine, highly-placed sources said on Saturday.
As reported by news agency PTI, the Pune-based drug firm submitted its application to the DCGI on Friday seeking permission for conducting the trials of the vaccine candidate 'Covishield'. According to the application, it would conduct an observer-blind, randomised controlled study to determine the safety and immunogenicity of 'Covishield' in healthy Indian adults. The firm said that an around 1,600 participants of more than 18 years would be enrolled in the study.
After reports in the medical journal The Lancet claimed the initial trial results showed that the vaccine was safe and prompted protective immune response, the firm plans to start phase II and III human trials in India in August.
At the same time, the Phase I human clinical trial of India's first indigenously-developed vaccine against novel coronavirus, COVAXIN, began at the AIIMS with the first dose of the injection given to a man, who is in his 30s. Already, over 3,500 volunteers have registered themselves for the trial, of whom the screening of at least 22 people is underway, said Dr Sanjay Rai, Professor at the Centre for Community Medicine at AIIMS and the principal investigator of the study.
The global race for vaccines is well and truly on. Last week, Michael Ryan, the head of emergencies at the World Health Organisation, had hailed "good news" from two COVID-19 vaccine candidates in early human trials, but warned that there was a long way to go. "We now need to move into larger-scale real-world trials. But it is good to see more data and more products moving into this very important phase of vaccine discovery," Ryan told reporters at a news conference. Ryan's comments came after scientists at Oxford University, in a paper published in the medical journal The Lancet, said their experimental vaccine had been shown to trigger a protective immune response in hundreds of people who got the shot. Also, in the journal, Chinese researchers from CanSino Biologics published a study on their experimental vaccine, which uses a similar technique as the Oxford team, that also reported an immune response.
Vaccine testing is a four-stage process—pre-clinical testing on animals; phase I clinical testing on a small group of people to determine its safety and to learn more about the immune response it provokes; phase II trials, or expanded safety trials, where dosage and frequency will be tested across wider cross-sections of the population; phase III large-scale tests where the vaccine is administered to thousands of people to confirm its efficacy. Phase I and phase II are the early trials, which will then be followed by a rigorous, intensive Phase III clinical testing, where the longevity of the vaccine response (whether the vaccine will last for long periods of time) will be analysed.
At the same time, a vaccine candidate under development by Pfizer Inc and Germany's BioNTech showed promise in a small, early study.
What do all these studies mean?
Let us take them one by one.
In The Lancet, Oxford University scientists said their vaccine candidate, prepared in partnership with the pharma giant AstraZeneca, appeared safe in the early trial phases, inducing a strong immune response within the body. Doses of the vaccine were given to 1,077 healthy adults aged between 18 and 55 in five UK hospitals in April and May as part of the phase I clinical trial and results. The results show they induced strong antibody and T-cell responses for up to 56 days after they were given. T-cells are immune responses by the body against the foreign virus, and are crucial for maintaining protection against the virus for longer periods of time.
"In addition, the strongest immune responses were produced in 10 participants who received two doses of the vaccine, indicating that this might be a good strategy for vaccination," said Andrew Pollard, chief investigator of the Oxford vaccine trial.
At the same time, a vaccine candidate under development by China's CanSino Biologics Inc and the country's military research unit, showed similar safe immune response in most of the 508 healthy volunteers.
Both the vaccine candidates (CanSino and Oxford-AstraZeneca) are adenoviral vector vaccines; that means they are prepared from a weakened, non-replicating version of a common cold virus that carries the coronavirus spike proteins into the human body, helping the immune system identify and build antibodies against the virus.
Both the studies reported adverse events such as fatigue, headache, and local tenderness, but found those to be tolerable and mostly ameliorated by paracetamol.
At the same time, Pfizer and BioNTech also released an early phase non-peer reviewed study which claimed that virus-neutralising antibodies were induced in 60 adults who were given two doses, a result in-line with a previous early-stage US trial. “These preliminary data are encouraging in that the vaccine is able to produce neutralising antibody responses in humans, and that it does so at relatively low dose levels,” Ugur Sahin, MD and CEO of BioNTech, said in a statement. The Pfizer-BioNTech candidate is an RNA vaccine. Here, no attenuated viruses are injected. Rather, a genetic code is introduced, which induces the human cells to create the foreign protein, alerting the immune system, and help the body recognise the entry of the virus in all its forms. The RNA vaccines are easier to make, but they are a new and unproven technology.
These studies come on the back of early phase results released by American biotech giant Moderna, which said their RNA vaccine prompted neutralising antibody activities in healthy adults, though it led to minor side effects in many patients.
Russia, meanwhile, has made progress with a vaccine developed by the Gamaleya Institute in Moscow—financed and backed by the Russian defence ministry. State-run news agency TASS had reported that the vaccine had “completed human trials” though it has only cleared Phase-I trials so far and is currently undergoing Phase-II trials. Russia’s deputy defence minister has said that this vaccine is “ready”, noting that of the two groups of volunteers who were administered the vaccine, all had built up immunity
Russian Health Minister Mikhail Murashko on Saturday said that the vaccine developed by the Gamaleya Institute, as well as a vaccine developed by the Vektor State Research Center of Virology and Biotechnology which was recently approved for clinical trials, were “neck and neck”.
Russia plans to begin mass production of the Gamaleya vaccine in August, with medical workers to start receiving the vaccine that very month. The vaccine will be “widely used in parallel with Phase III trials”, Murashko said.
Lastly, an RNA vaccine being developed by the Imperial College, London, showed promise when tested on mice, hwihc developed “highly-=specific” COVID-19 antibodies that were able to neutralise the virus. This vaccine has since been approved for human trials across England with trials on more than 200 people.
What are the challenges next?
Longevity of the vaccine effects will undoubtedly be the biggest challenge, which will be addressed in the phase III trials. “The vaccine developed by Oxford University has shown some positive signs of protection in the preliminary results of the early trial. It is being claimed that it will be more effective than others because it will develop antibodies and "natural killer cells" [T-cells] against SARS-COV2. But the biggest challenge would be the longevity of the [neutralising] antibodies,” Sunit K. Singh, professor and head, molecular biology, Institute of Medical Sciences, Banaras Hindu University told THE WEEK.
In SARS-CoV-2, antibodies are known to fade between three-six months, as reported by various studies, he said. “So what would be the fate of protection induced by a vaccine once the antibody response vanishes or is reduced? A virus of this kind will certainly need an attack from both sides—the antibodies and T-cells,” he added.
How are Indian pharma companies placed?
At least seven Indian pharma companies are working to develop a vaccine against coronavirus as they join global efforts to find a preventive to check the spread of the deadly virus that has already infected more than 14 million globally. Bharat Biotech, Serum Institute, Zydus Cadila, Panacea Biotec, Indian Immunologicals, Mynvax and Biological E are among the domestic pharma firms working on the coronavirus vaccines in India.
Bharat Biotech has received approval to conduct phase I and II clinical trial for its vaccine candidate COVAXIN, that has been developed and manufactured in the company's facility in Hyderabad. Last week, it started the human clinical trials.
Pharma major Zydus Cadila has said that it is looking to complete clinical trials of its COVID-19 vaccine candidate ZyCoV-D in seven months. The company had last week started clinical trials of its COVID-19 vaccine candidate with the first human dosing. Depending on the study outcomes, and if the data is encouraging, and the vaccine is found to be effective during the trials, it could take a total of seven months for the trials to be completed and for the vaccine to be launched, Zydus Cadila Chairman Pankaj R. Patel said in a statement.
Panacea Biotec in June said that it was setting up a joint venture firm in Ireland with US-based Refana Inc to develop a vaccine for COVID-19. The company, in partnership with Refana, aims to manufacture over 500 million doses of COVID-19 candidate vaccine, with over 40 million doses expected to be available for delivery early next year, Panacea Biotec had said.
Indian Immunologicals, a subsidiary of National Dairy Development Board (NDDB), has inked an agreement with Australia's Griffith University to develop a vaccine for coronavirus.
Others like Mynvax and Biological E are also working to develop vaccines for COVID-19.
-Inputs from Namita Kohli